Further characterization of a broad-spectrum antiviral substance in human serum

Abstract

A broadly active antiviral glycoprotein (UTI beta) occurs naturally in human sera at an average antiviral titer of 50 U/ml. This inhibitor is active against all virus families tested to date, including representative poxviruses, herpesviruses, enteroviruses, paramyxoviruses, alpha-viruses, flaviviruses, bunyaviruses, and rhabdoviruses. It is a glycoprotein of approximately 60,000 +/- 10,000 Da, which is stable at pH 2 to 10 and at 80 degrees C for up to 10 min. Mild oxidation with NaIO4 and treatment with glycosidases inactivates the material. Proteolytic degradation of the inhibitor molecule releases small active components of < 1000 Da, which retain antiviral activity. This activity of the small components has increased heat stability (120 degrees C for 15 min) and is inactivated by glycosidases. The antiviral activity thus appears to reside mainly in the oligosaccharide moiety of the glycoprotein. The inhibitor does not neutralize virions, but prevents attachment of most viruses to cells. These properties occur also in highly purified preparations. These findings indicate that human serum contains significant concentrations of a broadly active antiviral glycoprotein, which is distinct from interferon and other antiviral substances naturally found in human body fluids and tissues.